Is DSPP p.Ile131Thr (c.392T>C) pathogenic?

DSPP p.Ile131Thr (c.392T>C) is classified Benign in DSPP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0529); Common (popmax 8.1%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DSPP p.Ile131Thr (c.392T>C)?

AlphaMissense predicts likely benign (score 0.0529) — an in-silico prediction, not a clinical call.

DSPP p.Ile131Thr

Q: How common is DSPP p.Ile131Thr (c.392T>C) in the general population?

DSPP p.Ile131Thr (c.392T>C) is common (popmax 8.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.392T>C · rs61731009 · VCV787807

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0529 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.1%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0529	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4.5	GERP -3.3
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	0.002	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.1% African / African-American · 6,071/74,940 alleles

Filtering AF 7.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.86%

Overall 0.426% 6,880/1,613,856 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.1%	12
Admixed American	0.548%	182
Remaining individualsnot grpmax-eligible	0.525%	191
Middle Eastern	0.28%	357
South Asian	0.0253%	3,959
European (non-Finnish)	0.00949%	10,535

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DSPP
Protein: p.Ile131Thr
Coding: c.392T>C
dbSNP: rs61731009
Type: single nucleotide variant
Location: chr4:87612578 (GRCh38)

Full DSPP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dspp-p-ile131thr (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown